Albany 2001

Biomolecular
Stereodynamics
SUNY at Albany
June 19-23, 2001

Most of the 98.5% non-coding genomic DNA in mammals are retroposon-derived: genomic desert or repertoire?

Conversion of genetic information from RNA into DNA by reverse transcription is ancient and was instrumental for the transition from the RNP world to modern cells1. Surprisingly, in many eukaryotic lineages, the process of retroposition is still highly active. All types of RNAs2 can be reverse transcribed and their cDNA copies reintegrated into genomes as retronuons (a nuon is any stretch of a definable nucleic acid sequence3). About 42% of the human genome consists of discernible retronuons. If one extrapolates this figure to non-discernible retronuons (older than ~200 MY), it is conceivable that as much as 85% of the human genome may be retroposon-derived with the remainder ~3% DNA transposons and ~10% heterochromatin. Principally, this process leads to "junk DNA". However, mRNA-derived retronuons can give rise to active genes, often with different expression patterns, when compared to their respective founder genes3,4. Retronuons derived from small non-messenger RNAs (snmRNAs) generate novel snmRNA genes (such as neuron-specific BC1 and BC200 RNAs)2,3. Frequently, retronuons are exapted (co-opted) as regulatory elements that may alter expression or processing of targeted genes3,5 (for compilations see http://www-ifi.uni-muenster.de/exapted-retrogenes/tables.html). Consequently, retronuons are a major driving force of evolution. Comparison of the human genome with that of other mammals (mouse) or, particularly, chimpanzee, will reveal that neither contains numerous additional genes. Instead, we will observe exaptation of novel exons (often involving alternative splicing) from previously nonaptive intronic (as predicted by Gilbert6) or flanking sequences originally generated by retroposition. Furthermore, differential expression of shared genes with respect to developmental onset and/or cell-type specificity, often being triggered by de novo insertions of retronuons, will turn out to be a recurrent theme concerning species differences at the genomic level.